{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:18:14Z","timestamp":1760782694473},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"content-version":"vor","delay-in-days":4201,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopolymers"],"published-print":{"date-parts":[[1992,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In order to prevent enzymatic degradation of \u03b2\u2010casomorphin\u20105 (<jats:italic>1<\/jats:italic>) and morphiceptin, reduced peptide bonds were incorporated at the 2\u20133 and 3\u20134 bonds, respectively. The analogues were synthesized by a combination of solid phase methodology and reductive alkylation of resin\u2010bound peptide amines with Boc\u2010amino acid aldehydes (Boc: <jats:italic>tert<\/jats:italic>\u2010butyloxycarbonyl) in the presence of NaBH<jats:sub>3<\/jats:sub>CN. During reversed phase high pressure liquid chromatography purification, peak shape distortions could be observed. Epimerization was excluded, based on gas chromatography\/mass spectroscopy analysis, which indicated acceptable levels of racemization (&lt;3%) in the crude product. Instead, the phenomena could be attributed to slow <jats:italic>cis\/ trans<\/jats:italic> isomerizations originating from the Xxx\u2010Pro bonds in the sequence. The presence of different conformational isomers was also established by <jats:sup>1<\/jats:sup>H\u2010nmr spectroscopy in DMSO\u2010d<jats:sub>6<\/jats:sub>. All analogues showed high stability in blood plasma, enhanced binding affinity for the \u03bc receptor, and very low binding to the \u03b4 receptor. While the Phe<jats:sup>3<\/jats:sup>\u03a8(CH<jats:sub>2<\/jats:sub>\u2010<jats:italic>N<\/jats:italic>) Pro<jats:sup>4<\/jats:sup> analogues (<jats:italic>3<\/jats:italic>) and (<jats:italic>5<\/jats:italic>) displayed agonist activity, the Pro<jats:sup>2<\/jats:sup>\u03a8(CH<jats:sub>2<\/jats:sub>\u2010NH) Phe<jats:sup>3<\/jats:sup> modified analogue (<jats:italic>2<\/jats:italic>) showed antagonist activity comparable to <jats:sc>D<\/jats:sc>\u2010Phe\u2010Cys\u2010Tyr\u2010<jats:sc>D<\/jats:sc> \u2010Trp\u2010Arg\u2010Thr\u2010Pen\u2010Thr\u2010NH<jats:sub>2<\/jats:sub>.<\/jats:p>","DOI":"10.1002\/bip.360320807","type":"journal-article","created":{"date-parts":[[2004,12,30]],"date-time":"2004-12-30T03:00:26Z","timestamp":1104375626000},"page":"957-969","source":"Crossref","is-referenced-by-count":13,"title":["Morphiceptin and \u03b2\u2010casomorphin\u20105 analogues containing a reduced peptide bond: Selective \u03bc\u2010receptor agonists and a novel \u03bc antagonist, H\u2010Tyr\u2010Pro\u03c8(CH<sub>2<\/sub>\u2010NH)Phe\u2010Pro\u2010Gly\u2010OH"],"prefix":"10.1002","volume":"32","author":[{"given":"Nancy G. J.","family":"Delaet","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia M. F.","family":"Verheyden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Tourwe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Van Binst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peg","family":"Davis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas F.","family":"Burks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,2]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1515\/bchm2.1979.360.2.1211"},{"key":"e_1_2_1_3_2","first-page":"1217","volume":"360","author":"Henschen H.","year":"1979","journal-title":"Hoppe\u2010Seyler's Z. Physioi Chem."},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1515\/bchm2.1980.361.2.1835"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(81)90297-6"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(82)90017-1"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6259732"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)39296-7"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00507118"},{"key":"e_1_2_1_10_2","first-page":"72","volume":"37","author":"Hartrodt B.","year":"1982","journal-title":"Pharmazie"},{"key":"e_1_2_1_11_2","first-page":"165","volume":"37","author":"Hartrodt B.","year":"1982","journal-title":"Pharmazie"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(83)90463-0"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(84)90070-6"},{"key":"e_1_2_1_14_2","first-page":"271","volume":"43","author":"Mentz P.","year":"1988","journal-title":"Pharmazie"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(85)90049-X"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)60678-7"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3011.1986.tb01823.x"},{"key":"e_1_2_1_18_2","first-page":"233","volume-title":"Peptides, Chemistry Structure and Biology","author":"Hocart S. J.","year":"1990"},{"key":"e_1_2_1_19_2","volume-title":"Solid Phase Peptide Synthesis","author":"Stewart J. M.","year":"1984"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(87)90174-4"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)86120-2"},{"key":"e_1_2_1_22_2","doi-asserted-by":"crossref","unstructured":"Fehrentz J. A.&Castro B.(1983)Synthesis676.","DOI":"10.1055\/s-1983-30471"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)82959-2"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00168a025"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(00)94466-2"},{"key":"e_1_2_1_26_2","first-page":"7","volume":"21","author":"Liardon R.","year":"1984","journal-title":"Anal. Chem. Symp. Ser."},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/bscb.19911000506"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(00)81865-8"},{"key":"e_1_2_1_29_2","first-page":"112","volume-title":"Proceedings of the 20th European Peptide Symposium","author":"Gesquiere J. C.","year":"1989"},{"key":"e_1_2_1_30_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/0021-9673(89)90010-1","volume":"478","author":"Gesquiere J. C.","year":"1989","journal-title":"J. Chromatog."},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3011.1989.tb01506.x"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(00)90641-1"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)44165-2"},{"key":"e_1_2_1_34_2","first-page":"537","volume-title":"Proceedings of the 18th European Peptide Symposium","author":"Nishiuchi Y.","year":"1985"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.1981.360201209"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360311207"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3011.1991.tb01516.x"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.19.5871"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(83)90331-X"},{"key":"e_1_2_1_40_2","first-page":"544","volume":"249","author":"Kramer T.","year":"1989","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_1_41_2","first-page":"403","volume":"227","author":"Chang K.\u2010J.","year":"1983","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00119a019"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2364(85)90018-6"},{"key":"e_1_2_1_44_2","first-page":"6482","volume":"108","author":"Bothner\u2010By A. A.","year":"1984","journal-title":"J. Am. Chem. Soc."},{"key":"e_1_2_1_45_2","first-page":"6489","volume":"108","author":"M\u00fcller N.","year":"1986","journal-title":"J. Am. Chem. Soc."}],"container-title":["Biopolymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbip.360320807","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bip.360320807","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T19:34:28Z","timestamp":1698089668000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bip.360320807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,8]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1992,8]]}},"alternative-id":["10.1002\/bip.360320807"],"URL":"https:\/\/doi.org\/10.1002\/bip.360320807","archive":["Portico"],"relation":{},"ISSN":["0006-3525","1097-0282"],"issn-type":[{"value":"0006-3525","type":"print"},{"value":"1097-0282","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,8]]}}}